Results from a Phase 2b study of RTS,S/AS01 malaria vaccine in Kenyan adults have been published in The Journal of Infectious Diseases. The results indicate that the current malaria vaccines are likely not going to be effective enough at reducing infections among African adults to be included as part of a malaria elimination strategy in endemic countries. However, this does not change the fact that currently available malaria vaccines, when used alongside other preventative interventions such as bed nets, remain an effective intervention for reducing child deaths and the number of times children get malaria, including severe malaria, and ongoing vaccine implementation activities should continue as planned.
The vaccine efficacy results from this Phase 2b study in Kenyan adults were lower than from studies where malaria-naïve adults in the United States were vaccinated and subjected to controlled human malaria infection. For the adult study, a modest level of efficacy was observed in participants with active Plasmodium falciparum infections who were administered antimalarial drugs during the vaccination period. However, no vaccine efficacy was observed in adult participants who were free of P. falciparum infection at the study start and were also treated with antimalarial drugs. This study highlights the importance of conducting malaria vaccine clinical trials in target populations.
RTS,S is currently being implemented in African children (alongside the similar R21/Matrix-M malaria vaccine), who bear most of the burden of malaria, and has been shown to be safe and effective in these populations.
This study sought to establish malaria vaccine efficacy in African adults to determine whether vaccines like RTS,S can have a role in eliminating malaria-causing parasites in endemic countries. Adults living in these areas are typically resistant to disease due to naturally acquired immunity, but they often harbor infections that contribute to ongoing transmission. For a vaccine to contribute to malaria elimination, and ultimately global eradication, it would optimally provide a relatively high level of efficacy in preventing infection (not just disease) and be used in mass immunization campaigns for all age groups (similar to meningitis A campaigns in sub-Saharan Africa).
Previous studies have shown that the efficacy of RTS,S is lower in African adults than in malaria-naïve US adults. This may be due to concurrent exposure to P. falciparum infections in the African adults when they were vaccinated; there is some evidence that active or asymptomatic malaria infections may suppress the immune response to vaccines. Recent studies combining RTS,S with antimalarial drugs in young African children resulted in a synergistic effect in reducing malaria disease incidence.
The researchers working on this Phase 2b study tested a widely held assumption that antimalarial drugs given to adults could reverse this immunosuppression and enhance overall vaccine efficacy, and that the efficacy would be higher in RTS,S-immunized participants who tested negative for P. falciparum infection at the start of the study. The study results showed that these assumptions were incorrect.
“While the current study results are unable to explain why there was no efficacy in the group of participants who tested negative for P. falciparum at the study start, we believe this lack of efficacy is actually a clue in our attempt to understand why susceptibility to malaria varies among individuals despite similar exposure to the parasite,” said Dr. Cynthia Lee, the study lead and Project Director in the Bacterial & Parasitic Diseases Area at PATH’s Center for Vaccine Innovation and Access. “PATH is now conducting additional tests on the blood samples collected from these individuals to try to better understand the reasons behind their lower susceptibility to infection and their lack of vaccine efficacy.”
“This study will inform future studies that seek to explain the efficacy of various interventions such as vaccines that are focused on malaria parasite elimination, and ultimately global eradication,” said Prof. Elijah Songok, Director General of the Kenya Medical Research Institute (KEMRI).
The Phase 2b study enrolled 620 healthy Kenyan adults who were divided into five groups based on the presence or absence of P. falciparum infections at the start of the study. All participants received either RTS,S or rabies vaccine, which was used as the control comparator.
PATH was the study sponsor and conducted the study in collaboration with KEMRI, Walter Reed Army Institute of Research, and GSK. The study site was the KEMRI-Walter Reed Project’s Kombewa Clinical Research Center in Kisumu County, Kenya.
About malaria
Malaria is a life-threatening disease caused by Plasmodium parasites, which is spread to humans by some types of mosquitoes. There are five Plasmodium parasite species that cause malaria in humans. P. falciparum is the deadliest malaria parasite and the most prevalent on the African continent. Most deaths from malaria occur in children in sub-Saharan Africa.
Two vaccines—RTS,S/AS01 and R21/Matrix-M—are currently recommended by the World Health Organization for the prevention of P. falciparum malaria in children living in endemic areas of sub-Saharan Africa. Both vaccines are being implemented in many African countries with support from Gavi, the Vaccine Alliance. Both RTS,S and R21 have been shown to be safe and effective in preventing malaria in children and are expected to have a high public health impact.
About PATH
PATH is a global nonprofit dedicated to achieving health equity. With more than 40 years of experience forging multisector partnerships, and with expertise in science, economics, technology, advocacy, and dozens of other specialties, PATH develops and scales up innovative solutions to the world’s most pressing health challenges.
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